The objectives of this project are to study some of the factors which regulate erythropoietin production in three animal models: 1) protein defected rats, 2) rats which have had 5/6 of their renal mass removed, and 3) rats which have had 50-60% of their liver removed. We hope thereby to: 1) clarify the mechanism by which protein deprivation influences Ep production, and the role of altered protein metabolism in causing Ep levels and erythropoiesis to decline in various disease states; 2) to determine the changes which occur in erythropoietin responsive cells and extrarenal sites of erythropoietin production in response to uremia, and to test the efficacy of several therapeutic modalities for the anemia of renal failure; and 3) to determine the role of specific hepatic cells in the production of erythropoietin.